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Dr. Jervin Mano, MD
The Hidden Epidemic
Epidemiology of nosocomial infections Pathogens involved in nosocomial infection Therapeutic guidelines De-escalation approach Prevention
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Definition Incidence Historical milestones Classification Risk factors Mode of transmission Pathologic agents Drugs used Rx of common NI Prevention
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Nosocomial infection comes from Greek words “nosus” meaning disease and “ komeion” meaning to take care of - disease contracted by a patient while under medical care.
Also called as HOSPITAL ACQUIRED INFECTION
Infections are considered nosocomial if they first appear 48hrs or more after hospital admission or within 30 days after discharge.
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The incidence of NI is estimated at 5-10% in tertiary care hospitals reaching up to 28% in ICU.
One-third of nosocomial infections are considered preventable.
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Nosocomial infections are responsible for about 100,000 deaths per year in hospitals
The patients must stay in the hospital 4-5 additional days.
More than 70% of bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used in treatment
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New cutting edge diagnostic & therapeutic technologies for prolonging life
Population ages Compromised defenses
high prevalence of pathogens
high prevalence of immuocompromised hosts
efficient mechanisms of transmission from patient to patient.
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The famous ancient physician Charaka and surgeon Sushuruta (Ca. 400 B.C.) emphasized the need for prevention of infection in clinical practice
1800’s typhus was considered as HAI James Simpson (1830)-termed HAI Ingaz Semmelweiss (1861) emphasised importance of
hand hygiene in prevention of puerperal sepsis Lister introduced antiseptic theory Florence Nightingale “Do no harm”- Hospital hygiene.
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Alexander Fleming -Penicillin 1943- penicillin mass production 1943- Marybaber 1946- Pn resistant strains outnumbered
sensitive ones Pn resistant strains in Op patients 1960 – Methicillin Broad-spectrum antibiotics seemed to keep
check on S.aureus infections
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The Story Of Superbug
1961-MRSA Multiple drug resistant strains VRSA Superbugs today More recently the extensive use of indwelling medical devices
and the introduction of new antibiotics coupled with their indiscriminate use the gram-positive cocci have once again emerged as the predominant causes of infection
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Superbug Returns
Nonspecific
infections common among the normal population
they follow a current regional epidemiological situation
they do not need specific preventive arrangements
Specific
resulting from diagnostical or therapeutical procedures
due to lack of personal hygiene of staff,
wrong therapeutic technique
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Endogenous (50%) Exogenous (15%) Cross infection (35%)
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Patient Factors Immunocompromised Severity of illness Broken skin & mucous membrane Length of hospital stay
Iatrogenic factors Pathogens on hands of medical personal Invasive procedure Misuse of antibiotics Acquired antibiotic resistance
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Environmental Contaminated water systems
Nurse to patient ratio
Open beds close together
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There are five main modes of transmission
Contact
Vector borne
Air borne
Droplet
Common vehicle
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DROPLET TRANSMISSIONDroplet generated by sneezingCoughing or respiratory tract procedures like
Bronchoscopy or suction
VECTOR TRANSMISSIONTransmitted through insects andOther invertebrates animalssuch as mosquitoes and fleas.
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AIR BORNE TRANSMISSIONTiny droplet nuclei that remain (<5)suspended in air.
COMMON VEHICLE TRANSMISSIONTransmitted indirectly by materials contaminated with the infections.
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VIRUS
BACTERIA
FUNGI
Bacteria Commensal Bacteria
Staph.epidermidis (iv infections)
E. coli (UTI) Pathogenic Bacteria Gram-positive
Staph.aureus- In hospitals commonly 40-50% of S. aureus isolates are MRSA
Streptococci- Streptococcus beta-hemolyticus, Strept. Pyogenes
Clostridia sp
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Gram-negative Enterobacteriaceae (e.g. E. coli, Proteus, Klebsiella, Enterobacter,
Serratia marcescens)
Pseudomonas spp.
Legionella sp
VIRUS Hepatitis B,C
Respiratory Syncytial Virus
Rotavirus
Enterovirus
Varicella Zoster09-02-2017
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FUNGI
Candida albigans
Aspergillus spp.
Cryptococcus neoformans
Cryptosporidium
PARASITES
Pneumocystis carini
Toxoplasma pneumoniae
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90% due to bacteria 10% (others: virus, fungi, protozoal etc) Most common pathogens isolated from any HAI:
S. aureus (13%)
E. coli (12%)
CoNS (11%)
Enterococci (10%)
Pseudomonas (9%)
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Most common isolated pathogens also depends on site of infection
UTI (E. coli-24%)
SSI (S. aureus-20%)
BSI (CoNS-31%)
LRI (S. aureus 19%, Pseudomonas 17%)
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Urinary tract infections (34%) Surgical site infections (17%) Pneumonia (13%) Blood stream Infection (14%) Nosocomial diarrhea Fungal infections Legionellosis
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Cell wall/membrane synthesis inhibitors
Vancomycin
Cephalosporins
Carbapenems
Teicoplanin
Daptomycin
Piperacillin+tazobactum
Colistin
Protein synthesis Inhibitors
Aminoglycosides▪ Amikacin
▪ Netilmicin
▪ Tobramycin
Tigecycline
Linezolid
Quinpristin/Dalfopristin Miscellaneous
Levofloxacin
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Glycopeptide antibiotic MOA
inhibiting proper cell wall synthesis in Gm+ bacteria by preventing cross-linking
Antimicrobial spectrum MRSA & multi-resistant Staphylococcus epidermidis (MRSE) Clostridium difficile,Corynebacterium
Indications pseudomembranous colitis , MRSA infections
Adverse effects Red man syndrome Ototoxicity, Nephrotoxicity
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β-lactam antibiotic MOA: Inhibit cell wall synthesis Drugs:
Ceftazidime (3G) Cefepime (4G) Ceftaroline (5G)
AMS: Ceftazidime : Pseudomonas, Gm-ve bacilli Cefepime : Gm-ve bacilli, MRSA, Strep.pneumonia Ceftaroline : Gm+ve , MRSA, Penicillin resistant Strep.pneumonia,
Enterococcus
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Uses: Hospital acquired pneumonia
Hospital acquired bacteremia
Hospital acquired septicemia
UTIs
Febrile neutropenic pts (4G) ADR:
Hypersensitivity reactions
Superinfections
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β-lactam antibiotics Highly resistant to β-lactamases Broad spectrum antibiotic Drugs:
Imipenem
Meropenem
Ertapenem
Doripenem MOA: Inhibits cell wall synthesis Antimicrobial Spectrum:
Gm+ve, Gm-ve, Anareobes09-02-2017
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extremely potent broad spectrum antibiotic Indications:
Hospital acquired Infections- resistant to other β-lactam antibiotics
Inactivated by renal dehydropeptidase -> given in combination with cilastatin(inhibits the human enzyme dehydropeptidase)
ADR:
Decreases seizure threshold
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MEROPENEM Newer carbapenem not deactivated by dehydropeptidase Indications: -Reserve drug for serious HAI ADR: Similar to Imipenem but less potential to induce seizures
DORIPENAM ultra-broad spectrum Indications
complex abdominal infections Nosocomial pneumonia complicated UTI including kidney infections with septicemia
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Glycopeptide antibiotic MOA : inhibits cell-wall synthesis AMS :
MRSA Listeria monocytogenes,Corynebacterium spp,Clostridium spp Nonviridans and viridans streptococci, enterococci
Uses: MRSA and penicillin resistant Strep.infections Osteomyelitis, Enterococcal endocarditis
ADR : Hypersensitivity, Skin rashes, Neutropenia
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lipopeptide antibiotic MOA
inserted into cell membrane – creates hole – leakage of ions – depolarisation- cell death AMS: Gram-positive bacteria
glycopeptide-resistant Enterococci (GRE) MRSA, streptococci , corynebacteria.
Indications skin and skin structure infections caused by Gram-positive infections Staphylococcus aureus bacteraemia
Adverse effects Hypotension, Hypokalaemia, Hyperglycaemia Thrombocytopenia, Elevated creatine kinase
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Group: polypeptide antibiotic MOA : Binds to LPSs -> Disruption of cell membrane ->leakage of
intracellular contents -> bacterial death Antimicrobial Spectrum : Gm –ve bacteria
P. aeruginosa Acinetobacter species Enterobacteriaceae
Indications: VAP, Nosocomial bacteremia
ADR: Nephrotoxicity- Lesser toxic than aminoglycosides Neurotoxicity Bronchospasm (Inhalation)- treated with salbutamol
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Group : Aminoglycoside MOA: Bids to 50 S ribosome – inhibits protein synthesis Antimicrobial spectrum:
Pseudomonas aeroginosa
Proteus, Serratia, Klebsiella, Enterobacter, E.coli Indications
Serious Gm-ve HAI
M.tuberculosis ADR:
Ototoxicity, Nephrotoxicity
Neuromuscular blockade09-02-2017
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AMS: Aerobic Gm-ve bacilli Uses: Susceptible Enterobactericea, aerobic Gm-ve bacilli ADR: Similar to Amikacin but less toxic
Uses: Ps.aeuroginosa in combination with β-lactam antibiotics
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Tobramycin
Group: glycylcycline antibiotic MOA : bacteriostatic, broad spectrum antibiotic
Binds to 30S ribosome -> inhibits bacterial protein synthesis Antimicrobial Spectrum :
methicillin-resistant Staphylococcus aureus (MRSA)
Stenotrophomonas maltophilia
Haemophilus influenza
Neisseria gonorrhea
multi-drug resistant strains of Acinetobacter baumannii
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Indications: complicated intra-abdominal and skin and soft tissue
infections Adverse Effects : diarrhoea nausea and vomiting. pain at the injection site swelling and irritation; increased or
decreased heart rate and infections. Also avoid use in children and pregnancy, due to its effects on teeth and bone.
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Group : Oxazolidinone MOA : Binds to 50S ribosome -> inhibits bacterial protein synthesis Antimicrobial spectrum:
MRSA, VRSA, VRE
Strep.vidans, pneumonia
Corynebacterium, Clostridia Indications:
Nosocomial pneumonia
SSI ADR: Neutropenia
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Group: Streptogramins MOA: Binds to 50S ribosome -> inhibits bacterial protein synthesis AMA:
Gm +ve bacteria
M. pneumoniae, Legionella spp., and Chlamydia pneumoniae Indication :reserved for treatment of serious infections caused by
multiple-drug-resistant gram-positive organisms such as vancomycin-resistant E. faecium.
ADR : Arthralgia, myalgia, Phlebitis
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2G Fluoroquinolones MOA: Inhibition of bacterial enzyme – DNA gyrase, topoisomerase IV AMS:
Gm+ve esp. Strep.pneumonia Gm-ve bacilli Atypical pathogens- Chlamydia, Mycoplasma Anaerobes
Uses : C/c bronchitis Pneumonia (CA & HA) UTI A/c sinusitis
ADR: Tendonitis, Teratogenic
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Caspofungin Echinocandin
MOA: fungal cell wall lysis
Use : Aspergillus inf, Candidiasis
ADR: Abnormal liver fn Amphotericin B
Polyene- binds to ergosterol in cell wall-> increase permeability
Uses: invasive aspergillosis, histoplasmosis, Cocoidomycosis
ADR : Nephrotoxic
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Fluconazole
Azole- inhibits ergosterol synthesis
Uses: Candidiasis, Coiccoidomycosis
Adr: GI upset
Flucytosine
Inhibits fungal DNA syn
Use; in combi for candidiasis, Crytococcosis
ADR: Bone marrow deppresion
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It is the most common cause of nosocomial infections
80% of the infections are associated with indwelling catheters.
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Mild-Moderate Ciprofloxacin 500mg po / 400mg iv Q12H
Levofloxacin 500-750mg iv/po q24h
Ceftriaxone 1g iv
Severe Cefepime 2g iv q12h
Ceftazidime 2g iv q8h
Piperacillin+tazobactum 3.375-4.5giv q6h
Carbapenems
vancomycin
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Hooton TM. Nosocomial urinary tract infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. New York, NY: Churchill Livingstone; 2010:3725-3737
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Fluconazole 200-400mg/day x 14dif resistant
Oral flucytosine &/or Parenteral Amphotericin B Bladder irrigation with Amphotericin B is NOT recommended Fluconazole iv 200mg/day
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The incidence is increasing particularly for certain organisms such as multi resistance coagulase negative staphylococcus and candida.
Infections may occurs at the skin entry site of the IV device or in the sub cutaneous path of catheter.
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A thin coating containing biologically active agents, which coats the surface of structures such as teeth or the inner surfaces of catheter, tube, or other implanted or indwelling device. It contains viable and nonviable microorganisms that adhere to the surface and are trapped within a matrix of organic matter (for example, proteins, glycoproteins, and carbohydrates).
09-02-2017 Farlex Partner Medical Dictionary
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Simple Multi drug resistant
Coagulase –ve Staph. Semisynthetic Penicillins Vancomycin
Staph.aureus Penicillin, Cefazolin Vancomycin
Gm-ve FQ FQ+rifampin
Pseudomonas
Candidia Fluconazole Amphotericin_B
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They are also frequent
The definition is mainly clinical(purulent discharge around wounds
or the insertion site of drain, orspreading cellulites from wounds)
The infections can be exogenously or endogenously
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+ Vancomycin 1g iv Q12H
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Wound infection without sepsis ( not GIT, FGT) Mild-Moderate
Cephalexin 500mg po QID
Augmentin 875/125mg po BD
Doxycyline 100mg po BD Complicated
Ticarcillin + Clav 3.1g iv Q6H
Piptaz 3.375g iv Q6H
Ertapenem 1g Q24H
Wound infection with sepsis ( not GIT, FGT) Ampicillin + sulbactum 1.5-3g iv Q6H Ticarcillin + Clav 3.1g iv Q6H Piptaz 3.375g iv Q6H Cephazolin 1g iv Q8H
Wound Infection (GIT , FGT) Ampicillin + sulbactum 1.5-3g iv Q6H Ticarcillin + Clav 3.1g iv Q6H Piptaz 3.375g iv Q6H Ceftriaxone+metronidazole Imipenem 500mg iv Q6H
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Recommendations
Administer within 1 hour of incision to maximize tissue concentration
▪ Once the incision is made, delivery to the wound is impaired
Duration of prophylaxis
Stop prophylaxis
▪ within 24 hours after the procedure
▪ within 48 hours after cardiac surgery
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Bratzler et al Arch Surg 2005, 140:174-82
Harbarth S et al. Circulation 2000;101:2916–2921
Primary Alternate
Cardiac Cefazolin +/- Gentamicin Vancomycin +/- Gentamicin
GIT Cefazolin(or) Cefoxitin +/-Metronidazole
Clindamycin + Gentamicin
GUT Ampicillin +/- Gentamicin +/-Cefazolin
Clindamycin + Gentamicin
OBG Cefazolin Clindamycin + Gentamicin
Head & Neck Cefazolin Clindamycin + Gentamicin
Neurosurgery Cefazolin Vancomycin
Ophthal Gentamicin, tobramycin,Moxifloxacin, gatifloxacin
Ortho Cephazolin Clindamycin/ Vancomycin
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The most important are patients on ventilators in ICU.
Recent and progressiveradiological opacities of thepulmonary parenchyma, purulent sputum and recent onsite fever.
Most commonly caused by acinetobacter.
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Hospital-acquired pneumonia (HAP) Occurs 48 hours or more after admission, which was not incubating at the time of admission
Healthcare-associated pneumonia (HCAP) is defined as pneumonia that occurs in a non-hospitalized patient with extensive healthcare contact, as defined by one or more of the following: Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days. Residence in a nursing home or other long-term care facility Hospitalization in an acute care hospital for two or more days within the prior 90 days Attendance at a hemodialysis clinic within the prior 30 days
Ventilator-associated pneumonia (VAP) Arises more than 48-72 hours after endotracheal intubation
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Non-MDR Pathogens MDR Pathogens
Streptococcus pneumoniae Pseudomonas aeruginosa
Other Streptococcus spp. MRSA
Haemophilus influenzae Acinetobacter spp.
MSSA Antibiotic-resistant Enterobacteriaceae
Antibiotic-sensitive Enterobacteriaceae Enterobacter spp.
Escherichia coli ESBL-positive strains
Klebsiella pneumoniae Klebsiella spp.
Proteus spp. Legionella pneumophila
Enterobacter spp. Burkholderia cepacia
Serratia marcescens Aspergillus spp.
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Patients without Risk Factors for MDR Pathogens
Ceftriaxone (2 g IV q24h) or
Moxifloxacin (400 mg IV q24h), ciprofloxacin (400 mg IV q8h), or levofloxacin (750 mg IV q24h) or
Ampicillin/sulbactam (3 g IV q6h) or
Ertapenem (1 g IV q24h)
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Patients with Risk Factors for MDR Pathogens
1. A β-lactam:Ceftazidime (2 g IV q8h) or cefepime (2 g IV q8–12h) orPiperacillin/tazobactam (4.5 g IV q6h), Imipenem (500 mg IV q6h or 1 g IV q8h), or
meropenem (1 g IV q8h) plus
2. A second agent active against gram-negative bacterial pathogens:Gentamicin or tobramycin (7 mg/kg IV q24h) or amikacin (20 mg/kg IV q24h) orCiprofloxacin (400 mg IV q8h) or levofloxacin (750 mg IV q24h) plus
3. An agent active against gram-positive bacterial pathogens:Linezolid (600 mg IV q12h) orVancomycin (15 mg/kg, up to 1 g IV, q12h)
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Etiology : Cl. Difficle
Antibiotics associated : Clindamycin
Ampicillin
Cephalosporins
Fluoroquinolones Transmission
Acquired exogenously in hospitals
Transmitted through infected stools of patients or carriers
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Initial episode Mild to mod
Tab. Metronidazole 500mgTID X 10-14d Severe
Tab. Vancomycin 125mg QID X 10-14d Fulminant
Tab. Vancomycin 500mg + Inj. Metronidazole 500mgiv Q8H
+rectal instillation of Vancomycin (500mg in 100ml NS) as retention enema Q6-8H
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First : Similar to initial episode Second : Vancomycin tapering regime
125mg QID x 10-14d; BID x 7d ; OD x 7d ; Q2-3d x 2-8 weeks
Multiple :
Vancomycin tapering regime
Vancomycin 500mg QID x 10d + Saccharomyces boularetii 500mg BID x 28d
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Etiology:
Candida
Aspergillosis
Candida
Echinocandin : Caspofungin
Fluconazole
Amphotericin B
Fluconazole+Amphotercin B
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Aspergillosis
Voriconazole
Liposomal AMB
Caspofungin/Micafungin
Posiconazole
Itraconazole
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Hand washing Isolation Sterilization Gloves and aprons
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Prevention of Central Venous Catheter Infections Educate personnel about catheter insertion and care.
Use chlorhexidine to prepare the insertion site.
Use maximal barrier precautions during catheter insertion.
Consolidate insertion supplies (e.g., in an insertion kit or cart).
Use a checklist to enhance adherence to the bundle.
Cleanse patients daily with chlorhexidine.
Ask daily: Is the catheter needed? Remove catheter if not needed or used.
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Prevention of Ventilator-Associated Pneumonia and Complications Elevate head of bed to 30–45 degrees. Decontaminate oropharynx regularly with chlorhexidine. Give "sedation vacation" and assess readiness to extubate daily. Use peptic ulcer disease prophylaxis.
Prevention of Surgical-Site Infections Administer prophylactic antibiotics within 1 h before surgery; discontinue within
24 h. Limit any hair removal to the time of surgery; use clippers Prepare surgical site with chlorhexidine-alcohol. Maintain normal perioperative glucose levels (cardiac surgery patients)
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Prevention of Urinary Tract Infections Place bladder catheters only when absolutely needed (e.g., to relieve
obstruction), not solely for the provider's convenience.
Use aseptic technique for catheter insertion and urinary tract instrumentation.
Minimize manipulation or opening of drainage systems.
Ask daily: Is the bladder catheter needed? Remove catheter if not needed.
Prevention of Pathogen Cross-Transmission
Cleanse hands with alcohol hand rub before and after all contacts with patients or their environments.
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Razupenem 2G glycopeptides
Telavancin- sup. To Vancomycin in Rx MRSA Dalbavancin - sup. To Vancomycin in Rx catheter BSI Oritavancin – VRSA , VRE
Ramoplanin Cl.difficle, VRE
Torezolid Staph., Enterococci, More potent than Linezolid Phase III trial
Cephalosporins 5G Ceftobiprole
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The progressive emergence of gram-positive organisms as dominant isolates in nosocomial infections has become a primary health care concern
Antibiotic therapy regimens should balance the care of individual patients and the general patient population welfare.
Antibiotic treatment should start as soon as possible after infection is diagnosed and its duration should be minimized
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Monotherapy Conventional Combination Alternatives
E.coli Ceftazidime,CefepimeAmox-clav,FQ
Cefotaxime+ AmikacinPiperacillin+ Tazobactum
ImipenemImipenem+ AG/FQ
Klebsiella spSBL -
CeftazidimeCefipimeAmox-clav
Cefotaxime+ AmikacinPiperacillin+ Tazobactum
ImipenemImipenem+ AG/FQ
ESBL+ Imipenem,CefapimeFQ
Imipenem+AGPiperacillin+Tazobactum + Amikacin
Imipenem+FQ
Enterobacter
ImipenemCefapime,Piptaz
3G Cephalosporin+AG Imipenem+FQAG+FQ
Pseudomonas
Piperacillin3G,4G CephalosporinCarbapenem
Ticarcillin/ceftazidime+Sulbactum+AGCefftazidime+FQ
Piperacillin+FQAG+FQ
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Monotherapy Conventionall combinations
Alternatives
MRSA VancomycinImipenem+cilastinMeropenem
Vancomycin+FQRifampicin+Vancomycin
Imipenem+Vancomycin
Staphylococci(Coaagulase-ve)
VancomycinImipenem+cilastinMeropenem
Vancomycin+FQRifampicin+Vancomycin
Imipenem+FosfomycinAG
Entercoccus AmpicillinImipenemPiperacillinVancomycin
Ampicillin+GentamicinVancomycin+AG
Teicoplanin+ piperacillinImipenem +vancomycin
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Harrison’s principles of internal medicine , 18th edition Goodman and Gilman's the pharmacological basis of therapeutics 12th edition Atul Jain, Kanwardeep Singh, Vol. 9 No. 1, January-March 2007, Recent Advances in
the Management of Nosocomial Infections Basic & Clinical pharmacology , 12th Ed., Betram g. Katzung Leu HS, Huang CT. Clearance of funguria with short-course antifungal regimens: a
prospective, randomized, controlled study. Clin Infect Dis 1995;20:1152-7 Oxford textbook of medicine 4th edition Principles of Pharmacology 2nd edition, HL Sharma KK Sharma WHO Prevention of hospital-acquired infections 2nd Edition Prevention & Management of Catheter Associated UTI-Diane K. Newman http://www.optimusise.com/history-hospital-infection http://www.ncbi.nlm.nih.gov/pubmed/
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